title: Paternal aging and associated intraindividual alterations of global sperm 5-methylcytosine and 5-hydroxymethylcytosine levels.
abstract: OBJECTIVE
  To evaluate the relative intraindividual changes in sperm 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels associated with age and to compare the levels of 5-hmC in mature human sperm to blood DNA.
  
  
  METHODS
  Prospective research study.
  
  
  METHODS
  University-based andrology and in vitro fertilization (IVF) laboratory.
  
  
  METHODS
  Fifteen known fertile sperm donors, 22 other known fertile controls, and 41 male blood donors from a general population tissue bank.
  
  
  METHODS
  None.
  
  
  METHODS
  Measurements of global 5-mC and 5-hmC levels via an enzyme-linked immunosorbent assay (ELISA)-based assay.
  
  
  RESULTS
  Global sperm 5-mC levels exhibit a statistically significant increase with age, and a similar trend was seen in 5-hmC levels. On average, in the age ranges we analyzed, 5-mC increased by 1.76% per year, and 5-hmC, though more variable, increased by approximately 5% per year. Additionally, we found that 5-hmC levels in sperm are 32.59% of that found in blood DNA.
  
  
  CONCLUSIONS
  Global sperm DNA methylation patterns are stable over short periods of time but increase with age, which raises important questions regarding the risks of advanced paternal age. Additionally, as we would predict for a transcriptionally quiescent cell type, 5-hmC levels are statistically significantly lower in human sperm than in blood DNA.
authors.affiliation: Department of Surgery, Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Jenkins
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Aston
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Cairns
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Carrell
mesh_terms: D044503:5-Methylcytosine / Q000097:blood / Q000378:metabolism* / Q000031:analogs & derivatives; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D004247:DNA / Q000097:blood / Q000378:metabolism*; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D011446:Prospective Studies; D012307:Risk Factors; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; Advanced paternal age; global DNA methylation; sperm DNA methylation